RACS: Rapid Analysis of ChIP-Seq data for contig based genomes

Background: Chromatin immunoprecipitation coupled to next generation sequencing (ChIP-Seq) is a widely used technique to investigate the function of chromatin-related proteins in a genome-wide manner. ChIP-Seq generates large quantities of data which can be difficult to process and analyse, particularly for organisms with contig based genomes. Contig-based genomes often have poor annotations for cis-elements, for example enhancers, that are important for gene expression. Poorly annotated genomes make a comprehensive analysis of ChIP-Seq data difficult and as such standardized analysis pipelines are lacking. Methods: We report a computational pipeline that utilizes traditional High-Performance Computing techniques and open source tools for processing and analysing data obtained from ChIP-Seq. We applied our computational pipeline "Rapid Analysis of ChIP-Seq data" (RACS) to ChIP-Seq data that was generated in the model organism Tetrahymena thermophila, an example of an organism with a genome that is available in contigs. Results: To test the performance and efficiency of RACs, we performed control ChIP-Seq experiments allowing us to rapidly eliminate false positives when analyzing our previously published data set. Our pipeline segregates the found read accumulations between genic and intergenic regions and is highly efficient for rapid downstream analyses. Conclusions: Altogether, the computational pipeline presented in this report is an efficient and highly reliable tool to analyze genome-wide ChIP-Seq data generated in model organisms with contig-based genomes. RACS is an open source computational pipeline available to download from: https://bitbucket.org/mjponce/racs --or-- https://gitrepos.scinet.utoronto.ca/public/?a=summary&p=RACSComment: Submitted to BMC Bioinformatics. Computational pipeline available at https://bitbucket.org/mjponce/rac

Nucleus-specific linker histones Hho1 and Mlh1 form distinct protein interactions during growth, starvation and development in Tetrahymena thermophila

Chromatin organization influences most aspects of gene expression regulation. The linker histone H1, along with the core histones, is a key component of eukaryotic chromatin. Despite its critical roles in chromatin structure and function and gene regulation, studies regarding the H1 protein-protein interaction networks, particularly outside of Opisthokonts, are limited. The nuclear dimorphic ciliate protozoan Tetrahymena thermophila encodes two distinct nucleus-specific linker histones, macronuclear Hho1 and micronuclear Mlh1. We used a comparative proteomics approach to identify the Hho1 and Mlh1 protein-protein interaction networks in Tetrahymena during growth, starvation, and sexual development. Affinity purification followed by mass spectrometry analysis of the Hho1 and Mlh1 proteins revealed a non-overlapping set of co-purifying proteins suggesting that Tetrahymena nucleus-specific linker histones are subject to distinct regulatory pathways. Furthermore, we found that linker histones interact with distinct proteins under the different stages of the Tetrahymena life cycle. Hho1 and Mlh1 co-purified with several Tetrahymena-specific as well as conserved interacting partners involved in chromatin structure and function and other important cellular pathways. Our results suggest that nucleus-specific linker histones might be subject to nucleus-specific regulatory pathways and are dynamically regulated under different stages of the Tetrahymena life cycle.York University Librarie

The bromodomain-containing protein Ibd1 links multiple chromatin related protein complexes to highly expressed genes in Tetrahymena thermophila

Background: The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. Results: Using affinity purification coupled to mass spectrometry (AP-MS) we identified members of a SWI/SNF complex (SWI/SNFTt) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt, Swi1Tt, Swi3Tt, Snf12Tt, Brg1Tt, two proteins with potential chromatin interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals. SWI/SNFTt subunits localize exclusively to the transcriptionally active macronucleus (MAC) during growth and development, consistent with a role in transcription. While Tetrahymena Brg1 does not contain a BRD, our AP-MS results identified a BRD-containing SWI/SNFTt component, Ibd1 that associates with SWI/SNFTt during growth but not development. AP-MS analysis of epitope-tagged Ibd1 revealed it to be a subunit of several additional protein complexes, including putative SWRTt, and SAGATt complexes as well as a putative H3K4-specific histone methyl transferase complex. Recombinant Ibd1 recognizes acetyl-lysine marks on histones correlated with active transcription. Consistent with our AP-MS and histone array data suggesting a role in regulation of gene expression, ChIP-Seq analysis of Ibd1 indicated that it primarily binds near promoters and within gene bodies of highly expressed genes during growth. Conclusions: Our results suggest that through recognizing specific histones marks, Ibd1 targets active chromatin regions of highly expressed genes in Tetrahymena where it subsequently might coordinate the recruitment of several chromatin remodeling complexes to regulate the transcriptional landscape of vegetatively growing Tetrahymena cells.Comment: Published on BMC Epigenetics & Chromati

Use of Dark Chocolate for Diabetic Patients: A Review of the Literature and Current Evidence

Dietary changes are a major lifestyle factor that can influence the progression of chronic diseases such as diabetes. Recently, flavanols, a subgroup of plant-derived phytochemicals called flavonoids, have gained increasing attention, due to studies showing an inverse correlation between dietary intake of flavanols and incidence of diabetes. Flavanoids in the cocoa plant may ameliorate insulin resistance by improving endothelial function, altering glucose metabolism, and reducing oxidative stress. Oxidative stress has been proposed as the main culprit for insulin resistance. The well-established effects of cocoa on endothelial function also points to a possible effect on insulin sensitivity. The relationship between insulin resistance and endothelial function is a reciprocal one. Overall, the evidence from these studies suggests that cocoa may be useful in slowing the progression to type 2 diabetes and ameliorating insulin resistance in metabolic syndrome. Additionally, results from several small studies indicate that cocoa may also have therapeutic potential in preventing cardiovascular complications in diabetic patients. Studies highlighting the potential of cocoa-containing diets, in large-randomized controlled trials should be performed which might give us a better opportunity to analyze the potential health-care benefit for reducing the risk of complications in diabetic patients at molecular level

PMMA cranioplasty making by using open-source CAD software, PLA printers, and silicone rubber molds: technical note with two illustrative cases

No abstract available

2019 Mw 5.9 Mirpur, Pakistan Earthquake: Insights from Integrating Geodetic, Seismic, and Field Observations

On 24 September 2019, an Mw 5.9 earthquake struck near the Mangla reservoir in northeastern Pakistan and resulted in 39 fatalities and 746 serious injuries, making it the deadliest earthquake in the region since the 2005 Mw 7.6 Kashmir earthquake. Here, we integrate geodetic, seismic, and field observations to characterize the source properties and impact of the Mirpur earthquake as well as investigate whether it might be a reservoir‐induced event. From inverting Interferometric Synthetic Aperture Radar data, we find that a fault with strike ∼310°, dip ∼6°, and rake ∼117° is the optimal source, with slip concentrated between 5 and 6 km depth. This is consistent with our relocated aftershocks depth distribution and the lack of surface rupture observed in the field. Therefore, we infer that the earthquake ruptured the Main Himalayan Thrust (MHT). The event’s shallow depth might explain the extensive damage caused despite its moderate magnitude, with a maximum shaking intensity of VIII based on our field survey. The survey also revealed extensive damages associated with earthquake‐induced liquefaction. Our modeling shows that loading due to increased reservoir water level in the three months before the Mirpur earthquake led to Coulomb stress increase of ∼7–10 kPa on the rupture plane. However, this effect is ∼10 times smaller than the Coulomb stress increase due to the 2006 Mangla earthquake, and the Mirpur earthquake only occurred ∼1–2 weeks after peak water level. These suggest that pore pressure diffusion contributed to promoting the fault rupture at a time when it is close to failure due to accumulated stress from inter‐seismic loading. Because the Mirpur earthquake resulted in a stress increase of >0.2 MPa on the surrounding sections of the MHT and nearby faults, future rupture of these faults is a significant hazard and proper management of reservoir operations is necessary to prevent further elevating the seismic risk

Traffic flow prediction : an intelligent scheme for forecasting traffic flow using air pollution data in smart cities with bagging ensemble

Traffic flow prediction is the most critical part of any traffic management system in a smart city. It can help a driver to pick the most optimized way to their target destination. Air pollution data are often connected with traffic congestion and there exists plenty of research on the connection between air pollution and traffic congestion using different machine learning approaches. A scheme for efficiently predicting traffic flow using ensemble techniques such as bagging and air pollution has not yet been introduced. Therefore, there is a need for a more accurate traffic flow prediction system for the smart cities. The aim of this research is to forecast traffic flow using pollution data. The contribution is twofold: Firstly, a comparison has been made using different simple regression techniques to find out the best-performing model. Secondly, bagging and stacking ensemble techniques have been used to find out the most accurate model of the two comparisons. The results show that the K-Nearest Neighbors (KNN) bagging ensemble provides far better results than all the other regression models used in this study. The experimental results show that the KNN bagging ensemble model reduces the error rate in predicting the traffic congestion by more than 30%

Efficient removal of norfloxacin using nano zerovalent cerium composite biochar-catalyzed peroxydisulfate

Norfloxacin (NOR), an important antibiotic used for the treatment of different infections which is reportedly causing huge quantity of water pollution and severe environmental issues. In this study, biochar prepared from Phoenix dactylifera roots biomass (PB) and composited with mesoporous nano-zerovalent cerium (nZVCe) was used for treatment of NOR solutions. The various characterization and treatment studies showed successful formation of the nZVCe and PB composite. The nZVCe was found to improve physiological characteristics and catalytic efficiency of PB. The nZVCe/PB composite caused 52% removal of NOR as compared to 23% by the individual PB. The use of peroxydisulfate (PDS) with PB and nZVCe/PB showed further improvement in the removal of NOR and caused 58 and 84% removal efficiencies of NOR by PB/PDS and nZVCe/PB/PDS, respectively. The use of PDS with PB and nZVCe/PB was found to yield ●OH and SO4 ●– which improved degradation of NOR, however, addition of ●OH and SO4 ●– scavengers impeded NOR degradation. The PB was found to have several oxygen functional groups which decomposed PDS into ●OH and SO4 ●–. The nZVCe/PB showed high recovery, reusability, and stability and caused high removal of NOR even at fifth cycle of treatment both in the absence and presence of PDS. The treatment of NOR by nZVCe/PB-catalyzed PDS showed encouraging results under different pH, and varying concentrations of PDS, nZVCe/PB, and NOR as well as in real water samples which suggest potential practical applications of NOR contaminated water. Degradation of NOR resulted into several products and the resulting final product proved to be non-toxic

Functional Analysis of Hif1 Histone Chaperone in Saccharomyces cerevisiae

The Hif1 protein in the yeast Saccharomyces cerevisie is an evolutionarily conserved H3/H4-specific chaperone and a subunit of the nuclear Hat1 complex that catalyzes the acetylation of newly synthesized histone H4. Hif1, as well as its human homolog NASP, has been implicated in an array of chromatin-related processes including histone H3/H4 transport, chromatin assembly and DNA repair. In this study, we elucidate the functional aspects of Hif1. Initially we establish the wide distribution of Hif1 homologs with an evolutionarily conserved pattern of four tetratricopeptide repeats (TPR) motifs throughout the major fungal lineages and beyond. Subsequently, through targeted mutational analysis, we demonstrate that the acidic region that interrupts the TPR2 is essential for Hif1 physical interactions with the Hat1/Hat2-complex, Asf1, and with histones H3/H4. Furthermore, we provide evidence for the involvement of Hif1 in regulation of histone metabolism by showing that cells lacking HIF1 are both sensitive to histone H3 over expression, as well as synthetic lethal with a deletion of histone mRNA regulator LSM1. We also show that a basic patch present at the extreme C-terminus of Hif1 is essential for its proper nuclear localization. Finally, we describe a physical interaction with a transcriptional regulatory protein Spt2, possibly linking Hif1 and the Hat1 complex to transcription-associated chromatin reassembly. Taken together, our results provide novel mechanistic insights into Hif1 functions and establish it as an important protein in chromatin-associated processes